1. Field of the Invention
This invention relates to a microemulsifying system consisting essentially of coconut oil and Polysorbate 80 in a specific weight ratio. This invention also relates to microemulsion preconcentrates and microemulsions that contain a lipophilic functional ingredient formulated with the microemulsifying system, and to processes for preparing the microemulsion preconcentrates and microemulsions. The microemulsions can be used in the development and manufacture of new healthcare drinks.
2. Background Information
In order to ameliorate the oral bioavailability of coenzyme Q10 (CoQ10), P. Thanatuksorn et al. investigated five types of fats, four types of emulsifiers, and two types of aqueous phases (distilled water with or without 8 g/100 g w/w skim milk), and found that an optimal formulation was produced by virtue of the emulsion with coconut oil, a skim milk aqueous solution, and calcium stearoyl-2-lactate (CSL). Based on the results, P. Thanatuksorn et al. prepared a model CoQ10 product emulsified with coconut oil, 8 g/100 g w/w skim milk aqueous solution, and CSL, wherein 100 g of the emulsified CoQ10 product is composed of the following: 0.28 g of CoQ10, 0.8 g of CSL, 2.6 g of coconut oil, 14 g of sugar, 6.8 g of skim milk, and 75.52 g of water. The size of the oil droplets formed immediately after emulsification is 2.37±0.59 μm, and the oil droplets turned partially into a cream-like phase under the storage at 4° C. for 10 days. The oral bioavailability of the model CoQ10 product has been confirmed to be slightly greater than that of a standard commercial CoQ10 product (HJB CoenzymeQ10 EX; Fujitex Co., Ltd., Japan) (P. Thanatuksorn et al. (2009), LWT—Food Science and Technology, 42:385-390). In view of the foregoing, the model CoQ10 product prepared by P. Thanatuksorn et al. has a relatively large particle size, and the storage life at 4° C. is not sufficient.
Junya Hatanaka et al. utilized solubilizing agents commonly used as food ingredients to prepare new formulations of CoQ10, including a liquid formulation and a water-soluble powder formulation. The liquid formulation is a nano-emulsion (NE) which contains the following ingredients: based on a total of 100%, 10.5% of CoQ10, 12.0% of nonionic surfactants, 3% of soybean lecithin, 55% of glycerol, 15.0% of deionized water, and 4.5% of medium chain triglycerides (MCT), wherein the nonionic surfactants and soybean lecithin serve as an emulsifier, and MCT serves as an oil medium (Junya Hatanaka et al. (2008), International Journal of Pharmaceutics, 363:112-117). The components in the nonionic surfactants and MCT are not shown in the journal article. During the preparation of the aforesaid NE, i.e. CoQ10-NE, a large amount of glycerol and two different ingredients were required to serve as an emulsifier, and a homomixer and a high pressure homogenizer were required to achieve the complete emulsification of the formulation. The formation of the CoQ10-NE having particles with an average particle size of 60 nm might be accordingly facilitated, but the preparation process of the CoQ10-NE is complicated.
US 20060073176 A1 (corresponding to TW I321989 B) discloses a water-soluble composition containing CoQ10, which comprises (A) CoQ10 of 5 to 40% by weight, (B) monoester of polyglycerol with average polymerization degree of 10 and fatty acid having 18 carbon atoms of 5 to 30% by weight, (C) mono-, di-, tri- or penta-ester of polyglycerol with average polymerization degree of 3-6 and fatty acid having 18 carbon atoms of 1 to 18% by weight, and (D) water. It is asserted that the water-soluble composition containing CoQ10 has an average particle diameter of 110 nm or smaller. Even though it is mentioned in US 20060073176 A1 that a solvent such as oils is not needed to dissolve or disperse a high concentration of CoQ10 during the production of the water-soluble composition containing CoQ10, US 20060073176 A1 teaches not only that two kinds of surfactants are required to produce the water-soluble composition containing CoQ10, but also that a fifth component, i.e. (E) a solubilizer, including glucose-fructose liquid sugar, gum arabic, and reducing starch sugar, is required in some examples. Moreover, in some other examples, palm oil or sucrose acetic acid/isobutyric acid ester (SAIB) is even needed to serve as an oil component for forming an oil phase with CoQ10. During the production of the water-soluble composition containing CoQ10, a homomixer and a high pressure homogenizer are required to achieve the complete emulsification of the formulation, which results in an unsatisfactory production cost due to the use of such equipments.
US 20070259034 A1 discloses a crystal-free CoQ10 composition, which comprises CoQ10, a solvent, and a carrier oil. According to US 20070259034 A1, the solvent may be conjugated linoleic acid (CLA), a flax seed oil, an ethyl ester marine lipid, a citrus oil, or a combination thereof. Further, according to US 20070259034 A1, the carrier oil may be a flax seed oil, an organic flax seed oil which includes alpha linoleic acid (ALA), a soy lipid, a borage lipid, or a marine lipid. A marine lipid is a concentrate of ethyl ester EPA/DHA and can be 50% to 90% EPA/DHA combined. Still further, according to US 20070259034 A1, the CoQ10 composition further comprises a capric and caprylic glyceride, a vegetable monoglyceride, or a mixture of a vegetable monoglyceride and a diglyceride. Still yet further, according to US 20070259034 A1, the CoQ10 composition may be encapsulated into a softgel for oral administration. In view of the foregoing, the CoQ10 composition disclosed in US 20070259034 A1 is not suitable for use in the preparation of a healthcare product in liquid form, especially a healthcare drink.
US 20080145411 A1 discloses a composition for oral administration, which comprises an oxidized CoQ10, a lysolecithin, and an oil and fat. The weight ratio of a lysolecithin to an oxidized CoQ10 is not less than 0.7. A lysolecithin is a costly chemical substance, and the production cost would be increased when a lysolecithin is used. In addition, based on the examples given in US 20080145411 A1 as a whole, it is revealed that the composition for oral administration is not suitable for use in the preparation of a healthcare product in liquid form, especially a healthcare drink.
US 20080248013 A1 (corresponding to TW I351925 B) discloses a CoQ10-containing liquid composition which is obtained by dispersing and emulsifying CoQ10 in an aqueous liquid containing glycerin and a water-soluble substance. Specifically, the water-soluble substance consists of octenylsuccinate starch and dextrin. The liquid composition may be dried to form a CoQ10-containing solid composition. During the preparation of the liquid composition, a high pressure homogenizer is required to achieve the complete emulsification of the formulation, which results in an unsatisfactory production cost due to the use such an equipment. Moreover, the liquid composition as prepared in the examples of US 20080248013 A1 has a particle size not less than 0.3 μm, thereby being unable to meet the appearance requirement for the production of a drink.
US 20040152612 A1 discloses CoQ10-containing microemulsion preconcentrates and microemulsions. The microemulsion preconcentrates comprise a mixture consisting of the following: (a) a mixture consisting of a medium chain triglyceride and an omega-9 fatty acid and/or an omega-6 fatty acid, (b) a surface-active component comprising a surfactant of the polyoxyethylene type, and (c) a therapeutic active ingredient from the ubiquinone class, in particular CoQ10. In Example 1 of US 20040152612 A1, three microemulsion preconcentrates were prepared, and each of them is composed of the following components: (a) Miglyol□ 812 (a1) and oleic acid (a2) (which serves as an emulsifier or a solubilizing agent), (b) Tween 80 (b), and (c) CoQ10 (c1). In addition, the aforesaid three microemulsion preconcentrates contain either vitamin E (c2) or Cremophor EL (b2) (which serves as a solubilizing agent), and the weight ratio of component (b) to component (a) is about 1:1 or 9:7.
US 20040126367 A1 (corresponding to TW I334862 B) discloses a solution containing reduced CoQ10, wherein the reduced CoQ10 is coated with a liposome or solubilized or emulsified with a surfactant to stably maintain the reduced CoQ10 against oxidation. The substance used to prepare the liposome may be a phospholipid or glycolipid. The surfactant is preferably a nonionic surfactant, more preferably a polysorbate surfactant such as Tween 80 or the like, or polyoxyethylene hardened castor oil such as HCO-60 or the like. In Example 1 of US 20040126367 A1, the influence of the liposome on the oxidation stability of the reduced CoQ10 was evaluated via three types of lecithin. In Example 2 of US 20040126367 A1, the influence of the surfactant on the oxidation stability of the reduced CoQ10 was evaluated via Tween 80 and HCO-60 (an aqueous solution containing 1 wt % or 0.1 wt % of the surfactant). Preparation Example 2 of US 20040126367 A1 is a lotion containing the following ingredients: 1.0 wt % of Tween 80, 12.5 wt % of glycerol, 1.2 wt % of phosphatidyl choline, 0.1 wt % of reduced CoQ10, and purified water present in a sufficient amount such that the sum of the weight percents of all the ingredients is equal to 100.0 wt %.
US 20100284983 A1 (corresponding to TW 200715995 A) discloses a CoQ10-containing water-soluble composition, which comprises CoQ10, a hydrophilic polyglycerol fatty acid ester, a lipophilic sucrose fatty acid ester, and an aqueous phase component. The hydrophilic polyglycerol fatty acid ester is a decaglycerol mono-saturated fatty acid ester constituted of a fatty acid residue containing 12 or more carbon atoms. More preferably, the saturated fatty acid ester is at least one species selected from the group consisting of a laurate ester, a myristate ester and a palmitate ester. The lipophilic sucrose fatty acid ester is preferably an ester composed of higher fatty acid and acetic acid, and more preferably sucrose palmitate, sucrose stearate, and an acetylation product thereof. The amount of addition of the lipophilic sucrose fatty acid ester is preferably 1 to 200 parts by weight, more preferably 5 to 150 parts by weight, still more preferably 10 to 100 parts by weight, and particularly preferably 30 to 100 parts by weight to 100 parts by weight of CoQ10. The aqueous phase component contains a polyhydric alcohol and/or water. The polyhydric alcohol is preferably glycerol or sorbitol. During the production of the CoQ10-containing water-soluble composition, the components used must be warmed at a particular temperature (50 to 70° C.) so as to be dissolved, and a high pressure homogenizer is required to carry out the emulsification process.
US 20060051462 A1 discloses self emulsifying compositions for delivering lipophilic CoQ10 and other dietary ingredients. Since more than two different oil components and/or more than two different emulsifiers are used in the exemplary solution formulations given in the examples of US 20060051462 A1, use of such substances would certainly give rise to a high production cost. Furthermore, the properties of the aforesaid solution formulations disclosed in US 20060051462 A1 are unspecified.
Numerous exemplary liquid nanoemulsion concentrates are given in the examples of US 20090317532 A1. At least one oil component, at least one emulsion stabilizer, at least one surfactant, and even a co-surfactant are required to formulate these concentrates, which certainly results in a high production cost. In addition, during the generation of an oil phase and a water phase, heating must be conducted at 60° C. so that the ingredients used are miscible. Lastly, a high pressure homogenizer is required to conduct the emulsification process.
During the development of a stable microemulsion containing a lipophilic functional ingredient such as CoQ10, the applicant has found from the research thereof the following: even when co-surfactants (e.g. short-chain acids, alcohols, or fatty acids commonly used in the art) are dispensed with, and a high pressure homogenizer is not employed to conduct an emulsification process, a lipophilic functional ingredient such as CoQ10 can be uniformly dispersed in a aqueous medium at room temperature to form a stable microemulsion.